The effect of E. coli in mammals is dependent on the particular strain of organism. Many beneficial E. coli are present in the intestines. Since the initial association with diarrheal illness, five categories of diarrheagenic E. coli have been identified and are presently recognized: enterotoxigenic (ETEC), enteropathogenic (EPEC), enterohemorrhagic (EHEC), enteroaggregative (EAggEC), and enteroinvasive (EIEC). These categories are grouped according to characteristic virulence properties, such as elaboration of toxins and colonization factors and/or by specific types of interactions with intestinal epithelial cells. ETEC are the most common of the diarrheagenic E. coli and pose the greatest risk to travelers. E. coli of the family CS4-CFA/I are some of the more common enterotoxigenic E. coli. There is need for vaccines which are specific against this class of E. coli that give rise to antibodies that cross-react with and cross-protect against the more common members of the CS4-CFA/I family. There are six members of this family of ETEC fimbrial proteins, CFA/I, CS1, CS2, CS4, CS17 and PCF 0166. ETEC are responsible for high infant mortality in developing countries, with an estimate that almost 800,000 deaths per year due to these organisms. These organisms also cause illness in adult travelers to regions where the disease is endemic. No licensed vaccine exists against these organisms. The present vaccines being tested present problems related to manufacturing. So far, there has been no demonstration of significant efficacy of the prior art vaccines.
Colonization factor antigens (CFA) of ETEC are important in the initial step of colonization and adherence of the bacterium to intestinal epithelia. In epidemiological studies of adults and children with diarrhea, CFA/I is found in a large percentage of morbidity attributed to ETEC. The CFA/I is present on the surfaces of bacteria in the form of pili (fimbriae), which are rigid, 7 nm diameter protein fibers composed of repeating pilin subunits. The CFA/I antigens promote mannose-resistant attachment to human brush borders with an apparent sialic acid sensitivity. Hence, it has been postulated that a vaccine that establishes immunity against these proteins may prevent attachment to host tissues and subsequent disease.
Preferred that vaccines are those that give consistent protection and that are relatively inexpensive to manufacture. Immunization with a single antigen, either a peptide or individual denatured protein, that could simultaneously protect against organisms bearing this family of differing colonization factors is needed. Hence, it is desirable to identify peptides that do not rely on living organisms for production. Experimental evidence indicates that when animals are immunized with intact fimbriae, cross-reactivity is minimal.
Testing for CFA/I, CS1, CS2, CS3, CS4, CS5 and CS6 has been the most common diagnostic evaluation attempted. CFA/I, CS3 and CS6 may occur alone, but with rare exception CS1 is only found with CS3, CS2 with CS3, CS4 with CS6 and CS5 with CS6. These colonization factor-bearing (CF) organisms have been reported to account for up to 75% or as little as 23% of the ETEC, depending on location of the study.